The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target.

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a long non-coding RNA (lncRNA), is up-regulated in many solid tumors and associated with cancer metastasis and recurrence. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. In the present study, we evaluated the expression of MALAT1 by quantitative real-time PCR in 9 liver cancer cell lines and 112 HCC cases including 60 cases who received liver transplantation (LT) with complete follow-up data. Moreover, small interfering RNA (siRNA) was used to inhibit MALAT1 expression to investigate its biological role in tumor progression. We found that MALAT1 was up-regulated in both cell lines and clinical tissue samples. Patients with high expression level of MALAT1 had a significantly increased risk of tumor recurrence after LT, particularly in patients who exceeded the Milan criteria. On multivariate analysis, MALAT1 was an independent prognostic factor for predicting HCC recurrence (hazard ratio, 3.280, P = 0.003).In addition, inhibition of MALAT1 in HepG2 cells could effectively reduce cell viability, motility, invasiveness, and increase the sensitivity to apoptosis. Our data suggest that lncRNA MALAT1 play an important role in tumor progression and could be a novel biomarker for predicting tumor recurrence after LT and serve as a promising therapeutic target.

O-linked-ß-N-acetylglucosamine (O-GlcNAc) modification is a crucial post-translational modification. The enzymes responsible for the addition and removal of O-GlcNAc have been identified as O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In this study, O-GlcNAcylation level was examined in forty hepatocellular carcinoma (HCC) tissues of patients who underwent liver transplantation (LT) and ten healthy liver tissues by immunohistochemistry analysis. We also examined the expression of OGT and OGA in sixty HCC samples using real-time reverse-transcription polymerase chain reaction and analyzed their correlations with clinical parameters and prognosis in sixty HCC patients treated with LT. Additionally, the global O-GlcNAcylation level was altered through OGT and OGA silencing in the HCC cell line, and the effects of O-GlcNAcylation on cancer malignancy were investigated. We found that the global O-GlcNAcylation levels were significantly elevated in HCC tissues than that in healthy liver tissues (P = 0.031); moreover, O-GlcNAcylation was significantly enhanced in the tumor tissues of patients who had suffered from HCC recurrence after LT compared with those who had not (P = 0.046). Importantly, low expression of OGA was an independent prognostic factor for predicting tumor recurrence of HCC following LT (P = 0.041, hazard ratio, 0.438), especially in AFP low patients. In vitro assays demonstrated that O-GlcNAcylation play important roles in migration, invasion, and viability of HCC cells, partly through regulating E-cadherin, MMP1, MMP2, and MMP3 expression. Altogether, these results suggest that O-GlcNAcylation might play important roles in HCC formation and progression and may be a potential marker to predict patient risk of recurrence after LT and a valuable target for therapy.

Background & Aims Little is known about aetiology and morbidity and clinical characteristics of pyogenic liver abscess caused by extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae. Methods An analysis between pyogenic liver abscess patients caused by extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae isolates and those caused by non‐extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae was performed. Results Among 817 pyogenic liver abscess patients, there were 176 patients (21.5%) with pyogenic liver abscess of biliary origin, and 67 pyogenic liver abscess patients (8.2%) caused by extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae isolates (mainly Escherichia coli and Klebsiella pneumoniae). Of 176 pyogenic liver abscess patients related to biliary disorders, there were 48 pyogenic liver abscess patients (27.3%) caused by extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae. Within 67 pyogenic liver abscess patients caused by Enterobacteriaceae expressing extended‐spectrum beta‐lactamases, the occurrences of 48 pyogenic liver abscess patients (71.6%) were associated with biliary disorders. When compared with pyogenic liver abscess patients caused by non‐extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae, there were significantly greater incidences of polymicrobial infections, bacteremia, pulmonary infection, recurrence and death in pyogenic liver abscess patients caused by extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae. Carbapenems remain mainstay drugs against extended‐spectrum beta‐lactamase‐producing E. coli and K. pneumoniae. Independent risk factors for occurrence of pyogenic liver abscess caused by extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae were biliary disorders including extra‐ and intrahepatic cholangiolithiasis and an abnormal bilioenteric communication between bile and gut, a treatment history of malignancy such as operation and chemotherapy, pulmonary infection, and diabetes mellitus. Conclusions Pyogenic liver abscess caused by extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae isolates mainly occurs in patients with biliary disorders or with a treatment history of malignancy. The mainstay of treatment remains carbapenems in combination with adequate aspiration or drainage.